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化学抗原受体T细胞向细胞表面GRP78,有效地杀死质母细胞瘤和癌症干细胞

Shijie Wang¹, Wenwen Wei¹, Yuncang Yuan¹

¹Department of Targeting Therapy and Immunology and Laboratory of Animal Tumor Models, Cancer Center and National Clinical Research Center for Geriatrics and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Journal of translational medicine

|July 22, 2023

概括

化学抗原受体T (CAR-T) 细胞向细胞表面葡萄糖调节蛋白78 (csGRP78),有效消除质母细胞细胞,并抑制瘤生长. 这种新型免疫疗法对治疗具有攻击性的脑瘤具有极小副作用的前景.

科学领域:

在瘤学瘤学.
免疫治疗是一种免疫疗法.
分子生物学分子生物学

背景情况:

质母细胞瘤 (GBM) 是一种高度侵略性的脑瘤,预后不佳.
传统治疗提供了有限的生存益处,需要新的治疗策略.
在GBM中细胞表面葡萄糖调节蛋白78 (csGRP78) 的表达增加是一个潜在的治疗标.

研究的目的:

开发和评估用于质母细胞瘤治疗的针对csGRP78的化学抗原受体T (CAR-T) 细胞.
评估csGRP78向的CAR-T细胞的体外和体内疗效和安全性.

主要方法:

通过使用与csGRP78.8结合的来生成CAR-T细胞.
在GBM细胞系和质瘤干细胞 (GSCs) 上确认了csGRP78的局部化.
在实验室和体内使用异种移植模型对GBM细胞和GSC进行CAR-T细胞细胞毒性评估.

主要成果:

在GBM细胞系 (U-251MG,U-87MG) 和GSC中确认了csGRP78的表达.
由CAR-T细胞对GBM细胞和GSC进行特定杀死,由IFN-γ释放证明.
在体内观察到显著抑制瘤生长和减少GSCs,没有主要的器官毒性.

结论:

针对csGRP78的CAR-T细胞在体外和体内表现出强大的抗瘤活性,对抗GBM.
这种免疫治疗策略有效地抑制了质母细胞瘤的生长,具有有利的安全性.
csGRP78是开发针对GBM有效免疫疗法的有前途的治疗标.

关键词:

在CAR-T细胞中.在GBMGBMGBMGBMGBM 总书记会的总书记会的总书记会.在 csGRP78 中使用.

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